アラキドン酸5-リポキシゲナーゼ
- 関
- 5-lipoxygenase
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2013/12/05 07:41:40」(JST)
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Arachidonate 5-lipoxygenase |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
3O8Y, 3V92, 3V98, 3V99
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Identifiers |
Symbols |
ALOX5; 5-LO; 5-LOX; 5LPG; LOG5 |
External IDs |
OMIM: 152390 MGI: 87999 HomoloGene: 561 ChEMBL: 215 GeneCards: ALOX5 Gene |
EC number |
1.13.11.34 |
Gene Ontology |
Molecular function |
• arachidonate 5-lipoxygenase activity
• iron ion binding
• protein binding
• lipoxygenase activity
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Cellular component |
• nuclear envelope
• nuclear envelope lumen
• cytosol
• nuclear matrix
• nuclear membrane
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Biological process |
• leukotriene production involved in inflammatory response
• leukotriene metabolic process
• arachidonic acid metabolic process
• leukotriene biosynthetic process
• lipoxygenase pathway
• small molecule metabolic process
• lipoxin metabolic process
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Sources: Amigo / QuickGO |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
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Entrez |
240 |
11689 |
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Ensembl |
ENSG00000012779 |
ENSMUSG00000025701 |
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UniProt |
P09917 |
P48999 |
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RefSeq (mRNA) |
NM_000698 |
NM_009662 |
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RefSeq (protein) |
NP_000689 |
NP_033792 |
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Location (UCSC) |
Chr 10:
45.87 – 45.94 Mb |
Chr 6:
116.41 – 116.46 Mb |
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PubMed search |
[1] |
[2] |
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arachidonate 5-lipoxygenase |
Identifiers |
EC number |
1.13.11.34 |
CAS number |
80619-02-9 |
Databases |
IntEnz |
IntEnz view |
BRENDA |
BRENDA entry |
ExPASy |
NiceZyme view |
KEGG |
KEGG entry |
MetaCyc |
metabolic pathway |
PRIAM |
profile |
PDB structures |
RCSB PDB PDBe PDBsum |
Gene Ontology |
AmiGO / EGO |
Search |
PMC |
articles |
PubMed |
articles |
NCBI |
proteins |
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Arachidonate 5-lipoxygenase also known as 5-lipoxygenase or 5-LO is an enzyme that in humans is encoded by the ALOX5 gene.[1] Arachidonate 5-lipoxygenase is a member of the lipoxygenase family of enzymes. It transforms EFAs into leukotrienes and is a current target for pharmaceutical intervention in a number of diseases.
Contents
- 1 Substrates and products
- 2 Function
- 3 Clinical significance
- 4 Activation
- 5 Interactions
- 6 References
- 7 Further reading
- 8 External links
Substrates and products[edit]
EFA substrates and leukotriene products of 5-LO include:
- Arachidonic acid (AA) yields the 4-series leukotrienes (LTB4, LTC4, LTD4, LTE4 — generally proinflammatory)
- Eicosapentaenoic acid (EPA) yields the 5-series (LTB5, LTC5, LTD5, LTE5 — antiinflammatory)
- Gamma-linolenic acid (GLA via the DGLA intermediary) yields no leukotrienes, but inhibits the conversion of AA.
Function[edit]
5-LO catalyzes oxidation of AA at the 5-position to yield 5-hydroperoxyeicosatetraenoic acid (5-HPETE). 5-LO then converts 5-HPETE to leukotriene A4.[2]
Two other lipoxygenases, 12-LO and 15-LO, act at the 12- and 15-positions, yielding 12- and 15-HPETE. These pathways lead to the leukotriene 12-hydroxyeicosatetraenoic acid (12-HETE) and to the lipoxins, respectively.[3]
Clinical significance[edit]
5-LO is a target for pharmaceutical intervention in CAD.[4] Some people with variant alleles for 5-LO are at elevated risk for CAD.[5] 5-LO is expressed in brain cells and may participate in neuropathologic processes.[6]
Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined.[7]
5-LO inhibitors[edit]
As leukotrienes are important causes of pathological symptoms in asthma, 5-LO inhibitors were developed as asthma treatments. The only 5-LO inhibitor currently licensed for human use in asthma is Zileuton. Minocycline, although primarily a tetracycline antibiotic, is also a 5-LO inhibitor.[8] It may therefore be used as a DMARD-medication in mild rheumatoid arthritis and other rheumatic conditions.[9]
Hyperforin, an active constituent of the herb St John's wort, is a highly potent 5-LO inhibitor.[10]
Activation[edit]
5-LO is activated by 5-lipoxygenase activating protein (FLAP).
Interactions[edit]
Arachidonate 5-lipoxygenase has been shown to interact with Grb2[11][12] and COTL1.[13]
References[edit]
- ^ Funk CD, Hoshiko S, Matsumoto T, Rdmark O, Samuelsson B (April 1989). "Characterization of the human 5-lipoxygenase gene". Proc. Natl. Acad. Sci. U.S.A. 86 (8): 2587–91. doi:10.1073/pnas.86.8.2587. PMC 286962. PMID 2565035.
- ^ Reaction R01595 and R03058 at KEGG Pathway Database.
- ^ Dorlands Medical Dictionary, entries at arachidonate 5-lipoxygenase and following. Retrieved on 2006-02-07.
- ^ "5-Lipoxygenase, A New Therapeutic And Diagnostic Target For Heart Disease Management". UCLA Case No. 2001-429 PCT Publication Number: WO 03/035670 A2. Archived from the original on 2006-08-30. Retrieved 2007-11-18.
- ^ Dwyer JH, Allayee H, Dwyer KM, et al. (2004). "Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis". N. Engl. J. Med. 350 (1): 29–37. doi:10.1056/NEJMoa025079. PMID 14702425.
- ^ Zhang L, Zhang WP, Hu H, et al. (2006). "Expression patterns of 5-lipoxygenase in human brain with traumatic injury and astrocytoma". Neuropathology : official journal of the Japanese Society of Neuropathology 26 (2): 99–106. doi:10.1111/j.1440-1789.2006.00658.x. PMID 16708542.
- ^ "Entrez Gene: ALOX5 arachidonate 5-lipoxygenase".
- ^ can be used as DMARDS. Song Y, Wei EQ, Zhang WP, Zhang L, Liu JR, Chen Z (2004). "Minocycline protects PC12 cells from ischemic-like injury and inhibits 5-lipoxygenase activation". Neuroreport 15 (14): 2181–4. doi:10.1097/00001756-200410050-00007. PMID 15371729.
- ^ arthritis.about.com: Minocin - Minocycline - Dosage - Side Effects - Drug Interactions
- ^ Albert D, Zündorf I, Dingermann T, Müller WE, Steinhilber D, Werz O. (December 2002). "Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase". Biochemical Pharmacology. 15;64(12):1767-75. PMID 12445866
- ^ VanderNoot, V A; Fitzpatrick F A (September 1995). "Competitive binding assay of src homology domain 3 interactions between 5-lipoxygenase and growth factor receptor binding protein 2". Anal. Biochem. (UNITED STATES) 230 (1): 108–14. doi:10.1006/abio.1995.1444. ISSN 0003-2697. PMID 8585605.
- ^ Lepley, R A; Fitzpatrick F A (September 1994). "5-Lipoxygenase contains a functional Src homology 3-binding motif that interacts with the Src homology 3 domain of Grb2 and cytoskeletal proteins". J. Biol. Chem. (UNITED STATES) 269 (39): 24163–8. ISSN 0021-9258. PMID 7929073.
- ^ Provost, P; Doucet J, Hammarberg T, Gerisch G, Samuelsson B, Radmark O (May 2001). "5-Lipoxygenase interacts with coactosin-like protein". J. Biol. Chem. (United States) 276 (19): 16520–7. doi:10.1074/jbc.M011205200. ISSN 0021-9258. PMID 11297527.
Further reading[edit]
- Rådmark OP (2000). "The molecular biology and regulation of 5-lipoxygenase.". Am. J. Respir. Crit. Care Med. 161 (2 Pt 2): S11–5. PMID 10673219.
- Hammarberg T, Reddy KV, Persson B, Rådmark O (2003). "Calcium binding to 5-lipoxygenase". Adv. Exp. Med. Biol. Advances in Experimental Medicine and Biology 507: 117–21. doi:10.1007/978-1-4615-0193-0_19. ISBN 978-0-306-47283-1. PMID 12664574.
- Ishii S, Noguchi M, Miyano M, et al. (1992). "Mutagenesis studies on the amino acid residues involved in the iron-binding and the activity of human 5-lipoxygenase". Biochem. Biophys. Res. Commun. 182 (3): 1482–90. doi:10.1016/0006-291X(92)91901-2. PMID 1540191.
- Nguyen T, Falgueyret JP, Abramovitz M, Riendeau D (1991). "Evaluation of the role of conserved His and Met residues among lipoxygenases by site-directed mutagenesis of recombinant human 5-lipoxygenase". J. Biol. Chem. 266 (32): 22057–62. PMID 1939225.
- Hoshiko S, Rådmark O, Samuelsson B (1991). "Characterization of the human 5-lipoxygenase gene promoter". Proc. Natl. Acad. Sci. U.S.A. 87 (23): 9073–7. doi:10.1073/pnas.87.23.9073. PMC 55106. PMID 2251250.
- Matsumoto T, Funk CD, Rådmark O, et al. (1988). "Molecular cloning and amino acid sequence of human 5-lipoxygenase". Proc. Natl. Acad. Sci. U.S.A. 85 (1): 26–30. doi:10.1073/pnas.85.1.26. PMC 279474. PMID 2829172.
- Rouzer CA, Kargman S (1988). "Translocation of 5-lipoxygenase to the membrane in human leukocytes challenged with ionophore A23187". J. Biol. Chem. 263 (22): 10980–8. PMID 3134355.
- Dixon RA, Jones RE, Diehl RE, et al. (1988). "Cloning of the cDNA for human 5-lipoxygenase". Proc. Natl. Acad. Sci. U.S.A. 85 (2): 416–20. doi:10.1073/pnas.85.2.416. PMC 279559. PMID 3422434.
- Jakobsson PJ, Shaskin P, Larsson P, et al. (1995). "Studies on the regulation and localization of 5-lipoxygenase in human B-lymphocytes". Eur. J. Biochem. 232 (1): 37–46. doi:10.1111/j.1432-1033.1995.tb20778.x. PMID 7556168.
- Janssen-Timmen U, Vickers PJ, Wittig U, et al. (1995). "Expression of 5-lipoxygenase in differentiating human skin keratinocytes". Proc. Natl. Acad. Sci. U.S.A. 92 (15): 6966–70. doi:10.1073/pnas.92.15.6966. PMC 41452. PMID 7624354.
- Lepley RA, Fitzpatrick FA (1994). "5-Lipoxygenase contains a functional Src homology 3-binding motif that interacts with the Src homology 3 domain of Grb2 and cytoskeletal proteins". J. Biol. Chem. 269 (39): 24163–8. PMID 7929073.
- Shaw KJ, Ng C, Kovacs BW (1994). "Cyclooxygenase gene expression in human endometrium and decidua". Prostaglandins Leukot. Essent. Fatty Acids 50 (5): 239–43. doi:10.1016/0952-3278(94)90160-0. PMID 8066098.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Woods JW, Evans JF, Ethier D, et al. (1993). "5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes". J. Exp. Med. 178 (6): 1935–46. doi:10.1084/jem.178.6.1935. PMC 2191287. PMID 8245774.
- Mancini JA, Li C, Vickers PJ (1994). "5-Lipoxygenase activity in the human pancreas". Journal of lipid mediators 8 (3): 145–50. PMID 8268460.
- VanderNoot VA, Fitzpatrick FA (1996). "Competitive binding assay of src homology domain 3 interactions between 5-lipoxygenase and growth factor receptor binding protein 2". Anal. Biochem. 230 (1): 108–14. doi:10.1006/abio.1995.1444. PMID 8585605.
- Brock TG, McNish RW, Bailie MB, Peters-Golden M (1997). "Rapid import of cytosolic 5-lipoxygenase into the nucleus of neutrophils after in vivo recruitment and in vitro adherence". J. Biol. Chem. 272 (13): 8276–80. doi:10.1074/jbc.272.13.8276. PMID 9079648.
- Nassar GM, Montero A, Fukunaga M, Badr KF (1997). "Contrasting effects of proinflammatory and T-helper lymphocyte subset-2 cytokines on the 5-lipoxygenase pathway in monocytes". Kidney Int. 51 (5): 1520–8. doi:10.1038/ki.1997.209. PMID 9150468.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
External links[edit]
- Arachidonate 5-Lipoxygenase at the US National Library of Medicine Medical Subject Headings (MeSH)
Oxidoreductases: monooxygenases (EC 1.13)
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1.13.11: two atoms of oxygen |
- lipoxygenase: Arachidonate 5-lipoxygenase
- Arachidonate 12-lipoxygenase/ALOX12
- Arachidonate 8-lipoxygenase
- Arachidonate 15-lipoxygenase/ALOX15
- Linoleate 11-lipoxygenase
- other dioxygenase: Catechol dioxygenase
- Homogentisate 1,2-dioxygenase
- Cysteine dioxygenase
- 4-Hydroxyphenylpyruvate dioxygenase
- Indoleamine 2,3-dioxygenase
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1.13.12: one atom of oxygen |
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1.13.99: other |
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- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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Carrier proteins, metalloproteins: iron-binding proteins
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heme |
- Ferritin (Bacterioferritin)
- Lactoferrin
- Transferrin
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nonheme |
- Hemerythrin
- Inositol oxygenase
- Iron-sulfur protein
- Lipoxygenase
- Tyrosine hydroxylase
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Metabolism: lipid metabolism - eicosanoid metabolism enzymes
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Precursor |
- Phospholipase C
- Diacylglycerol lipase
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Prostanoids |
- PGE synthase
- Prostaglandin-E2 9-reductase
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Leukotrienes |
- 5-Lipoxygenase activating protein/Arachidonate 5-lipoxygenase
- LTA4 hydrolase (B4 synthesis)
- LTC4 synthase
- Gamma-glutamyl transpeptidase
- DPEP2
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Ungrouped |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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UpToDate Contents
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English Journal
- Metabolomic and transcriptomic profiling of human K-ras oncogene transgenic rats with pancreatic ductal adenocarcinomas.
- Yabushita S, Fukamachi K, Tanaka H, Fukuda T, Sumida K, Deguchi Y, Mikata K, Nishioka K, Kawamura S, Uwagawa S, Suzui M, Alexander DB, Tsuda H.SourceEnvironmental Health Science Laboratory, Sumitomo Chemical Co., Osaka 554-8558, Japan.
- Carcinogenesis.Carcinogenesis.2013 Jun;34(6):1251-9. doi: 10.1093/carcin/bgt053. Epub 2013 Feb 7.
- Pancreatic ductal adenocarcinoma (PDAC) is one of the most debilitating malignancies in humans, and one of the reasons for this is the inability to diagnose this disease early in its development. To search for biomarkers that can be used for early diagnosis of PDAC, we established a rat model of hum
- PMID 23393225
- OXER1, a G protein-coupled oxoeicosatetraenoid receptor, mediates the survival-promoting effects of arachidonate 5-lipoxygenase in prostate cancer cells.
- Sarveswaran S, Ghosh J.SourceVattikuti Urology Institute, Henry Ford Health System, Detroit, MI 48202, United States.
- Cancer letters.Cancer Lett.2013 May 2. pii: S0304-3835(13)00361-3. doi: 10.1016/j.canlet.2013.04.027. [Epub ahead of print]
- Inhibition of 5-Lox induces apoptosis in prostate cancer cells by inactivating PKCε which is prevented by 5-oxoETE, and activators of PKCε prevent 5-Lox inhibition-induced apoptosis, suggesting that 5-Lox metabolites exert survival signaling via PKCε. However, mechanisms by which 5-Lox metabolite
- PMID 23643940
- Overexpression of 5-lipoxygenase and its relation with cell proliferation and angiogenesis in 7,12-dimethylbenz(α)anthracene-induced rat mammary carcinogenesis.
- Chatterjee M, Das S, Roy K, Chatterjee M.SourceChemical Carcinogenesis and Chemoprevention Laboratory, Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India.
- Molecular carcinogenesis.Mol Carcinog.2013 May;52(5):359-69. doi: 10.1002/mc.21858. Epub 2011 Dec 28.
- The present study was performed to investigate the critical role of 5-lipoxygenase (5-LOX) in 7,12-dimethylbenz(α)anthracene (DMBA)-induced rat mammary inflammation associated carcinogenesis. Female Sprague-Dawley rats at 50 days of age were treated with 7,12-dimethylbenz(α)anthracene (DMBA; 0.5 m
- PMID 22213124
Japanese Journal
- Expression Analysis of Leukotriene-Inflammatory Gene Interaction Network in Patients with Coronary Artery Disease
- , , , ,
- Journal of Atherosclerosis and Thrombosis 21(4), 329-345, 2014
- … We aimed to construct a network of interactions between leukotrienes and inflammatory biomarkers and evaluate the expression of key members of the leukotriene pathway and leukotriene-induced inflammatory molecules in patients with coronary artery disease(CAD) and healthy controls.Methods: Leukotrienes and their regulatory inflammatory molecules reported in the literature were used to construct a biological network employing Gene spring GX v12.5. …
- NAID 130004444722
- Preliminary assessment of differential expression of candidate genes associated with atherosclerosis
- , , [他], , ,
- Genes & Genetic Systems 88(3), 199-209, 2013
- … 11 candidate genes, namely tumor protein (TP53), transforming growth factor, beta receptor II (TGFBR2), cysthathionenine-beta-synthase (CBS), insulin receptor substrate 1 (IRS1), lipoprotein lipase (LPL), methylenetetrahydrofolate reductase (MTHFR), thrombomodulin (THBD), lecithin-cholesterol acyltransferase (LCAT), matrix metallopeptidase 9 (MMP9), low density lipoprotein receptor (LDLR), and arachidonate 5-lipoxygenase-activating protein (ALOX5AP) genes associated with …
- NAID 130003361009
- Detection of 5-Lipoxygenase Activity in the Liverwort Marchantia polyrnorpha L.
- , ,
- Bioscience, biotechnology, and biochemistry 73(11), 2549-2551, 2009-11-23
- … We detected 5-LOX (arachidonate 5-lipoxygenase) in the homogenate of <I>Marchantia polymorpha</I> … LC/MS/MS analysis indicated that the liverwort 5-LOX produced 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HPETE) with arachidonic acid as a substrate. … The 5-LOX activity showed a Ca<SUP>2+</SUP> …
- NAID 10027548337
Related Links
- Arachidonate 5-lipoxygenase also known as 5-lipoxygenase or 5-LO is an enzyme that in humans is encoded by the ALOX5 gene. Arachidonate 5- lipoxygenase is a member of the lipoxygenase family of enzymes. It transforms EFAs into ...
- アラキドン酸-5-リポキシゲナーゼ(arachidonate 5-lipoxygenase)は、アラキドン酸 代謝酵素の一つで、次の化学反応を触媒する酸化 ... 反応式の通り、この酵素の基質は アラキドン酸とO2、生成物は(5S,6S,7E,9E,11Z,14Z)-5,6-エポキシイコサ-7,9,11,14- ...
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★リンクテーブル★
[★]
- 英
- arachidonate 5-lipoxygenase
- 関
- 5-リポキシゲナーゼ
[★]
アラキドン酸、アラキドン酸エステル
- 関
- AA、arachidonic acid
[★]
リポキシゲナーゼ, 不飽和脂肪酸酸化酵素, LOX